Relationship between the changes of ER, PR, Her-2 and Ki-67 before and after neoadjuvant chemotherapy and chemotherapy efficacy in breast cancer
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摘要:
目的 探讨乳腺癌患者在新辅助化疗(NAC)前后雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(Her-2)和增殖相关抗原(Ki-67)的变化与新辅助疗效相关性。 方法 收集2020年1月1日—2021年12月31日于蚌埠医科大学附属第一医院接受新辅助化疗的100例乳腺癌患者的资料，最终有80例患者纳入研究。NAC方案采用蒽环类联合紫杉类方案，Her-2阳性型患者NAC方案为多西他赛+卡铂+曲妥珠单抗+帕妥珠单抗(TCbHP)。NAC结束后所有患者均行乳腺癌手术治疗，对术后肿瘤残留样本进行免疫组织化学检测，并记录相关指标的表达变化。根据Miller-Payne系统分级及术后病理结果，将患者分为病理完全缓解组(pCR)和非病理完全缓解组(non-pCR)。采用χ2检验和多因素logistic回归模型分析non-pCR组ER、PR、Her-2以及Ki-67在化疗前后的表达差异，并分析分子的表达变化是否与患者疗效相关。 结果 在NAC前后ER、PR、Her-2和Ki-67变化率分别为2.50%、7.50%、10.00%和40.00%。NAC前后Ki-67(P=0.011)表达变化比较差异有统计学意义，而ER(P=0.737)、PR(P=0.581)、Her-2(P=0.108)表达变化比较差异均无统计学意义。此外，多因素分析表明，Ki-67高表达是新辅助化疗临床疗效的独立预测因子(P＜0.05)。 结论 NAC治疗可能会影响Ki-67表达水平，而ER、PR和Her-2未发生明显变化。NAC后Ki-67表达水平降低的患者可能有更好的疗效。 Abstract:Objective To investigate the relationship between the changes of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2(Her-2) and proliferation-associated antigen (Ki-67) in breast cancer patients before and after neoadjuvant chemotherapy (NAC). Methods The data of 100 patients with breast cancer who received neoadjuvant chemotherapy in the First Affiliated Hospital of Bengbu Medical University from January 1, 2020 to December 31, 2021 were collected. Finally, 80 patients were included in the study. The NAC regimen used anthracycline combined with taxoid regimen, and the NAC regimen for Her-2 positive patients was docetaxel+carboplatin+trastuzumab+pertuzumab (TCbHP). After NAC, all patients underwent surgery for breast cancer. Immunohistochemical tests were performed on postoperative tumor residual samples, and the expression changes of related indicators were recorded. According to the grading of Miller-Payne system and postoperative pathological results, the patients were divided into pathologically complete response group (pCR) and non-pathologically complete response group (non-pCR). χ2 test and multiple logistic regression model were used to analyze the differences in the expression of ER, PR, Her-2 and Ki-67 before and after chemotherapy in the non-PCR group, and to analyze whether the expression changes of these molecules were correlated with the disease control rate of patients. Results The change rates of ER, PR, Her-2 and Ki-67 before and after NAC were 2.50%, 7.50%, 10.00% and 40.00%, respectively. There were statistically significant differences in the expression changes of Ki-67 (P=0.011) before and after NAC, while there were no statistically significant differences in the expression changes of ER (P=0.737), PR (P=0.581) and Her-2 (P=0.108). In addition, multiple logistic regression analysis showed that Ki-67 high expression was an independent predictor of clinical disease control rate of neoadjuvant chemotherapy (P < 0.05). Conclusion NAC treatment may affect Ki-67 expression, while ER, PR and Her-2 do not change significantly. Patients with reduced Ki-67 expression levels after NAC may have a higher rate of disease control. -
表 1 80例乳腺癌患者临床病理资料
Table 1. Clinicopathological data of 80 patients with breast cancer
项目 例数(%) 项目 例数(%) 年龄 疗效评价 ≤35岁 1(1.25) 部分缓解 60(75.00) >35岁 79(98.75) 病情稳定 20(25.00) 分子分型 疾病进展 0 Luminal A型 2(2.50) ER Luminal B型 51(63.75) 阳性 56(70.00) Her-2型 18(22.50) 阴性 24(30.00) 三阴型 9(11.25) PR 化疗方案 阳性 36(45.00) TEC 60(75.00) 阴性 44(55.00) TCbHP 20(25.00) Her-2 手术方式 阳性 20(25.00) 改良根治术 70(87.50) 阴性 60(75.00) 保乳术 5(6.25) Ki-67 改良根治术+乳房重建整形术 5(6.25) 高表达 56(70.00) 低表达 24(30.00) 
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表 2 NAC对ER、PR、Her-2和Ki-67的影响
Table 2. Effects of NAC on ER, PR, Her-2, and Ki-67
分子标志物 阳性→阴性(例) 阴性→阳性(例) 变化(例) 不变(例) 改变率(%) ER 2 2 4 76 2.50 PR 2 4 6 74 7.50 Her2 3 5 8 72 10.00 Ki-67 28a 4b 32 48 40.00 注：a为高表达→低表达，b为低表达→高表达。
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表 3 ER、PR、Her-2和Ki-67的变化情况(例)
Table 3. Changes in ER, PR, Her-2, and Ki-67(cases)
分子标志物 表达情况 NAC前后不变 NAC前后改变 χ2值 P值 ER 阳性 54 2 1.210 0.737 阴性 22 2 PR 阳性 34 2 2.850 0.581 阴性 40 4 Her-2 阳性 17 3 2.500 0.108 阴性 55 5 Ki-67 高表达 28 28 9.600 0.011 低表达 20 4
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表 4 变量赋值情况
Table 4. Variable assignment
变量 赋值方法 ER 阳性to阳性=(0, 0, 0)，阳性to阴性=(1, 0, 0)，阴性to阳性=(0, 1, 0)，阴性to阴性=(0, 0, 1)；以阳性to阳性为参照。 PR 阳性to阳性=(0, 0, 0)，阳性to阴性=(1, 0, 0)，阴性to阳性=(0, 1, 0)，阴性to阴性=(0, 0, 1)；以阳性to阳性为参照。 Her-2 阳性to阳性=(0, 0, 0)，阳性to阴性=(1, 0, 0)，阴性to阳性=(0, 1, 0)，阴性to阴性=(0, 0, 1)；以阳性to阳性=(0, 0, 0)为参照。 Ki-67 Ki-67＜30%=1，Ki-67≥30%=2 疗效 部分缓解=0，病情稳定=1
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表 5 ER、PR、Her-2和Ki-67与疾病控制率的logistic回归分析
Table 5. Logistic regression analysis of ER, PR, Her-2, Ki-67, and disease control rate
变量 B SE Waldχ2 P值 OR值 95% CI ER(阳性to阴性) -1.529 1.566 0.953 0.329 0.217 0.010~4.669 ER(阴性to阳性) -0.825 0.993 0.690 0.406 0.438 0.063~3.069 ER(阴性to阴性) -1.864 1.279 0.350 0.534 0.512 0.075~2.054 PR(阳性to阴性) 1.724 1.572 1.203 0.273 5.606 0.258~121.998 PR(阴性to阳性) 0.664 1.100 0.365 0.546 1.943 0.225~16.770 PR(阴性to阴性) -1.803 1.095 0.411 0.650 0.354 0.201~13.110 Her-2(阳性to阴性) -2.911 1.890 2.373 0.123 0.054 0.001~2.209 Her-2(阴性to阳性) -3.431 1.901 3.258 0.071 0.032 0.001~1.343 Her-2(阴性to阴性) -1.514 2.438 0.386 0.535 0.220 0.002~26.175 Ki-67 2.638 1.150 5.260 0.022 13.988 1.468~133.310
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